DNA sequencing is becoming a major factor in a number of different emerging scientific fields. For example, DNA sequencing has been utilized in an attempt to diagnosis various diseases. One known method of performing such DNA sequencing/analysis is by matching an array of known DNA sequences (referred to as probes) with an unknown target DNA. More specifically, such a process typically includes placing a number of known DNA sequences on a glass slide. Each of the known DNA sequences are placed at a specific geographic location on the glass slide. A typical glass slide may have the capability of containing 50,000 individual locations, thereby allowing for processing of 50,000 DNA sequences.
Once the known DNA probes are placed in the predetermined locations on the slide, an unknown sample of DNA is placed on the slide. After a set period of time, if the unknown sample of DNA matches any of the known DNA sequences, the unknown DNA sample will hybridize with the known DNA sequence at the given location of the known DNA sequence. Assuming there is a match, the unknown sample DNA is identified as the DNA sequence with which the hybridization occurred.
In accordance with the foregoing technique, it is necessary to determine whether hybridization has occurred as well as the specific location of the hybridization so as to allow for a correlation between the location of the hybridization and the corresponding known DNA sequence. One common method of performing this determination is by an optical detection technique. In accordance with this technique, first, after allowing sufficient time for hybridization between the known DNA sequences and the unknown sample DNA, the slide is treated such that all un-hybridized DNA are removed from the slide. Next, an optical detection technique is utilized to determine the presence of a fluorescent molecule, which is attached to each known DNA sequence prior to the hybridization process. Specifically, if hybridization has occurred, the fluorescent molecule (i.e., die) attached to the known DNA sequence will be present even after the known DNA sequence has hybridized with the unknown DNA sample (if there was no match, all the known DNA sequences along with the fluorescent molecule would be removed from the slide during the aforementioned treatment process). Accordingly, by utilizing, for example, a laser and a photo detector, it is possible to determine the presence and location of the fluorescent molecule, which identifies the sample DNA by correlating the position of the fluorescent molecule with the location of the known DNA sequences. Typically, the instrument utilized to determine the presence of the fluorescent molecule is a desktop micro-array scanner.
Specific examples of such known optical detection systems and methods are set forth in U.S. Pat. No. 5,578,832, “Method And Apparatus For Imaging A Sample On A Device” issued to Trulson et al., and U.S. Pat. No. 5,631,734, “Method And Apparatus For Detection Of Fluorescently Labeled Materials”, issued to Stem et al. Both of the foregoing patents are hereby incorporated by reference. Utilizing a method similar to that described above both of the foregoing patents employ the use of a fluorescent molecule, such as fluorophore and biotin, which is attached to the known DNA sequence. An optical system is then utilized to determine whether hybridization has occurred by measuring fluorescence activated between the sample DNA and the known DNA.
Another known technique for identifying unknown DNA sequences is disclosed in U.S. Pat. No. 6,203,983, which is also hereby incorporated by reference. As disclosed therein, a method is presented which allows for the detection of a chemical interaction (e.g., DNA hybridization) without having to modify (i.e., label) the known DNA sequence. Specifically, the method entails formation of a mechanical cantilever mechanism capable of physical movement in the upward and downward direction. The cantilever mechanism is arranged in conjunction with the sample DNA and known DNA such that hybridization of the DNA will result in the physical deflection of the cantilever, which can be detected, thereby allowing for identification of the sample DNA.
Notwithstanding the foregoing chemical interaction detection systems utilized to identify unknown DNA samples, problems remain. For example, the systems utilizing optical detection means to detect fluorescent markers can be expensive. Moreover, the time requirements for operating the system can be exceedingly long as a typical array to be analyzed may contain on the order of 50,000 DNA samples, which need to be scanned on a one-by-one basis during processing. Systems utilizing micromechanical devices, such as the cantilever mechanism disclosed in the '983 patent, require elaborate semiconductor processing techniques during the formation thereof, which increase the costs associated with the resulting test arrays. Moreover, such devices are exceedingly subject to failure due to mechanical nature of the operation of the array, thereby reducing the overall reliability of the resulting array.
Accordingly, there remains a need for providing a detection system capable of identifying unknown DNA samples that eliminates the need for the optical scanner so as to allow for a reduction in both the time and cost associated with performing the analysis. In addition, it is desirable that the detection system eliminate the need for micromechanical devices so as to improve the overall reliability of the system.
It is the object of the present invention to correct the foregoing deficiencies in the prior art.